Natto, a fermented food made from boiled soybeans, has been eaten for more than 1000 years in Asia. The fermentation microbe isolated from natto is the Gram-positive endospore-forming bacterium Bacillus subtilis natto (formerly designated Bacillus natto). Nattokinase is an extracellular enzyme secreted by B. subtilis natto and belongs to the alkaline serine protease family, the catalytic center of which contains three conserved residues, Asp-32, His-64, and Ser-221. It has a molecular mass of 27.7 kDa and an isoelectric point of 8.7. Nattokinase is composed of 275 amino acids, and the gene sequence is homologous to those of other members of the subtilisin family (99.5% homology with subtilisin E, 86% with subtilisin BPN′, and 72% with subtilisin Carlsberg). It not only degrades fibrin in thrombi but also cleaves plasminogen activator inhibitor type I.
Nattokinase has greater thrombolytic activity than plasmin, a natural thrombolytic protease in blood, and increases the production of plasmin from plasminogen due to its action on plasminogen activator. These observations, together with the fact that it can be absorbed across the intestinal tract after oral administration and induce fibrinolysis, make nattokinase a potential clot-dissolving agent for the treatment of cardiovascular disease. Dietary supplementation with natto suppresses the intimal thickening of arteries and leads to the lysis of mural thrombi seen after endothelial injury. Other clinically thrombolytic agents, such as urokinase and streptokinase, are costly and unstable in the intestinal tract. The use of oral administration of nattokinase in fibrinolytic therapy for thrombosis and the prevention of atherosclerosis is therefore of interest. Nattokinase is currently used as a nutrient supplement to improve circulation in the body. Although much research has been carried out on nattokinase, there has been no interest in whether it can degrade amyloids, which are also highly insoluble and protease resistant.